Eplerenone restores 24-h blood pressure circadian rhythm and reduces advanced glycation end-products in rhesus macaques with spontaneous hypertensive metabolic syndrome

Sci Rep. 2016 Apr 1:6:23957. doi: 10.1038/srep23957.

Abstract

Hypertension is often associated with metabolic syndrome (MetS), and serves as a risk factor of MetS and its complications. Blood pressure circadian rhythm in hypertensive patients has been suggested to contribute to cardiovascular consequences and organ damage of hypertension. But circadian changes of BP and their response to drugs have not been clearly investigated in non-human primates (NHPs) of MetS with hypertension. Here, we identified 16 elderly, hypertensive MetS rhesus monkeys from our in-house cohort. With implanted telemetry, we investigate BP changes and its circadian rhythm, together with the effect of antihypertensive drugs on BP and its diurnal fluctuation. MetS hypertensive monkeys displayed higher BP, obesity, glucose intolerance, and dyslipidemia. We also confirmed impaired 24-h BP circadian rhythm in MetS hypertensive monkeys. Importantly, Eplerenone, a mineralocorticoid receptor blocker, exerts multiple beneficial effects in MetS hypertensive monkeys, including BP reduction, 24-h BP circadian rhythm restoration, and decreased plasma concentration of inflammation factors and advanced glycation end-products. In summary, we identified a naturally-developed hypertensive MetS NHP model, which is of great value in the studies on pathogenesis of MetS-associated hypertension and development of novel therapeutic strategies. We also provided multiple novel mechanistic insights of the beneficial effect of Eplerenone on MetS with hypertension.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anesthesia, General
  • Animals
  • Antihypertensive Agents / pharmacology*
  • Antihypertensive Agents / therapeutic use
  • Blood Pressure / drug effects*
  • Blood Pressure / physiology
  • Circadian Rhythm / drug effects*
  • Drug Evaluation, Preclinical
  • Eplerenone
  • Glycation End Products, Advanced / blood*
  • Hypertension / blood
  • Hypertension / drug therapy*
  • Macaca mulatta
  • Metabolic Syndrome / blood
  • Metabolic Syndrome / drug therapy*
  • Mineralocorticoid Receptor Antagonists / pharmacology*
  • Mineralocorticoid Receptor Antagonists / therapeutic use
  • Models, Animal
  • Spironolactone / analogs & derivatives*
  • Spironolactone / pharmacology
  • Spironolactone / therapeutic use
  • Telemetry
  • Wakefulness

Substances

  • Antihypertensive Agents
  • Glycation End Products, Advanced
  • Mineralocorticoid Receptor Antagonists
  • Spironolactone
  • Eplerenone